Phenotypic comparison and the potential antitumor function of immortalized bone marrow-derived macrophages (iBMDMs).

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.

[First trimester and second-trimester integrated screening for Down's syndrome].

OBJECTIVE: To evaluate the effect of first and second-trimester integrated screening so as to provide an efficient screening protocol for Down's syndrome. METHODS: Using the dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA), the freeßhCG (beta human chorionic gonadotropin), PAPP-A (pregnancy associated plasma protein-A) and NT (nuchal translucency) value of type B ultrasound were assayed in the pregnancy serum during the first trimester (11-13W(+6) d) and free ßhCG and AFP (alpha fetoprotein) during the second trimester(15-20W(+6) d). By the risk calculation software, the risks during both trimesters and their integrated risk were calculated for each patient respectively. Amniocentesis and venepuncture were employed for diagnosing the high-risk patients (> 1/270). Electronic network follow-up was carried out after delivery. RESULTS: In a total of 4237 pregnant women, 98 were found to carry a high risk during the first trimester, 241 during the second trimester and 101 during the integrated screening respectively. And 2, 3 and 4 cases were diagnosed with Down's symptom at a detection rate of 50%, 75% and 100% and a detection efficiency of 1:50, 1:80 and 1:25 respectively. CONCLUSION: Integrated screening is superior to either the first or second-trimester screening. With a lower false positive rate and a higher detection rate, it reduces the chance of invasive puncture. Advanced type B ultrasonic technology is needed to improve the first-trimester diagnostic efficiency and to develop a better integrated screening protocol.

Influence of epidural dexamethasone on maternal temperature and serum cytokine concentration after labor epidural analgesia.

OBJECTIVE: To evaluate the effects of epidural dexamethasone on maternal temperature and serum cytokine levels after labor epidural analgesia. METHODS: Sixty healthy term nulliparas in spontaneous labor were randomized to receive epidural analgesia alone using bupivacaine 0.125% and fentanyl 1 µg/mL (group I) or epidural analgesia combined with dexamethasone 0.2mg/mL (group II) (n=30 per group). Maternal tympanic temperature was measured before epidural analgesia and hourly thereafter until delivery. Maternal and cord venous blood were sampled for analysis of interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-10 levels. RESULTS: There was no difference in the incidence of intrapartum fever (38 °C or more) between the 2 groups (3/30 versus 1/30, P=0.612). The mean maternal temperature increased with time in group I, with the elevation reaching statistical significance at 4 hours post analgesia and at delivery compared with baseline (P=0.012 and P=0.043, respectively). A similar trend was observed with maternal serum IL-6 levels in group I. In group II, maternal temperature and IL-6 levels did not differ from baseline at any time point during labor. CONCLUSION: Epidural dexamethasone alleviates maternal temperature elevation after epidural analgesia. This effect can be attributed to the decrease in IL-6 levels.